Plasma and joint tissue pharmacokinetics of two doses of oral cannabidiol oil in guinea pigs (Cavia porcellus).

Cannabidiol (CBD) has gained widespread popularity as a treatment for osteoarthritis (OA) in pets; however, there is minimal scientific evidence regarding safe and effective dosing. This study determined plasma and tissue pharmacokinetics after oral CBD oil suspension administration in Hartley guinea pigs (Cavia porcellus), which spontaneously develop OA at 3 months of age. Ten, 5-month-old, male guinea pigs were randomly assigned to receive 25 (n = 5) or 50 mg/kg (n = 5) CBD oil once orally. Blood samples were collected at 0, 0.25, 0.5, 1, 2, 4, 8, 12, and 24 h timepoints. Open-field enclosure monitoring revealed no adverse effects. After euthanasia, stifle cartilage and infrapatellar fat pads were collected to quantitate CBD. CBD concentrations were determined using a validated liquid chromatography-mass spectrometry method, and pharmacokinetic parameters were calculated using noncompartmental analysis. The area under the plasma concentration-versus-time curve was 379.5 and 873.7 h*ng/mL, maximum plasma concentration was 42 and 96.8 ng/mL, time to maximum plasma concentration was 1.6 and 4.8 h, and terminal phase half-life was 8.1 and 10.8 h for the 25 and 50 mg/kg doses, respectively. CBD was detected in joint tissues of all animals. Further studies, including work in female guinea pigs, are needed to determine the efficacy of CBD for OA.

Optimization of overhead enclosure monitoring in juvenile male Dunkin Hartley guinea pigs (Cavia porcellus).

Overhead enclosure monitoring provides objective quantitative mobility measurements for animals undergoing open-field testing. Notably, protocols for testing optimization have been minimally established for the guinea pig. It is unknown whether (a) repeated exposure, (b) time-of-day, or (c) length of testing duration influence outcome parameters. We hypothesized that guinea pigs would display decreased activity following repeated exposure to the open field; heightened activity during the earliest testing period; and that 10 min would be adequate for data collection. The study was conducted in two separate phases to distinguish between enclosure habituation and time-of-day effects, respectively. Two cohorts of male Dunkin Hartley guinea pigs were allowed voluntary movement in an open-field enclosure for 14 min to quantify mobility outcomes, including total distance traveled, total time mobile, average speed while mobile, and total time spent in the shelter. For both phases, testing occurred at four different times of day, and overhead monitoring software was programmed to divide the total testing duration into 2-min bins. Habituation phase results showed time mobile and distance traveled were influenced significantly by repeat exposure, as animals were most active during the first testing event. Time-of-day phase animals spent significantly more time mobile during the earliest testing period. Interestingly, significant differences were observed across 2-min bins for the time-of-day phase but not during the habituation phase. Specifically, progressively decreased ambulatory activity was observed as testing duration increased. Thus, habituation and time-of-day should be accounted for when possible. Finally, a trial period greater than 10 min may not yield additional data.

Comparison of two point of care lactate instruments in guinea pigs (Cavia porcellus).

Background: Lactate measurements have been utilized as diagnostic and prognostic tools for a variety of veterinary species. Reference intervals for lactate have not been published or validated in guinea pigs. Methods: Whole blood from 48 anesthetized laboratory guinea pigs (46 Dunkin Hartley [38 males, eight females]; two Strain 13 [two males]) was analyzed using two point of care instruments (iSTAT and Lactate Plus). There were two consecutive timepoints on the iSTAT (iSTAT time 1 and time 2) and three consecutive timepoints on the Lactate Plus (Lactate Plus time 1, time 2, and time 3). Results: There was agreement with no constant or proportional bias between the two instruments compared at equivalent timepoints (iSTAT time 1 and Lactate Plus time 3) as determined by Bland-Altman (bias: -0.19; 95% LoA: -0.55 to 0.16) and Deming linear regression analyses (slope: 1.092, 95% confidence intervals (CI): -0.9 to 1.29; y-intercept: 0.09, 95% CI: -0.12 to 0.30). Reference intervals for iSTAT time 1 were 0.49 to 1.83 mmol/L and Lactate Plus time 1 were 0.60 to. 2.2 mmol/L. There was a significant increase in lactate values from iSTAT time 1 to iSTAT time 2 and from Lactate Plus time 1 to Lactate Plus time 3. Conclusions and Clinical Relevance: This study found strong agreement between the point of care instruments. Reference intervals for lactate for both the iSTAT and Lactate Plus instruments were similar to canine and feline intervals. Analysis should occur within 5 minutes of sample collection. Future work should assess lactate as a prognostic indicator in guinea pigs.

Evaluation of electroacupuncture for symptom modification in a rodent model of spontaneous osteoarthritis.

OBJECTIVE: Faced with the frustration of chronic discomfort and restricted mobility due to osteoarthritis (OA), many individuals have turned to acupuncture for relief. However, the efficacy of acupuncture for OA is uncertain, as much of the evidence is inconclusive. The purpose of this study was to evaluate electroacupuncture (EA) in a rodent model of OA such that conclusions regarding its effectiveness for symptom or disease modification could be drawn. METHODS: Ten 12-month-old male Hartley guinea pigs-which characteristically have moderate to advanced OA at this age-were randomly assigned to receive EA for knee OA (n = 5) or anesthesia only (control group, n = 5). Treatments were performed three times weekly for 3 weeks, followed by euthanasia 2 weeks later. Gait analysis and enclosure monitoring were performed weekly to evaluate changes in movement. Serum was collected for inflammatory biomarker testing. Knee joints were collected for histology and gene expression. RESULTS: Animals receiving EA had significantly greater changes in movement parameters compared to those receiving anesthesia only. There was a tendency toward decreased serum protein concentrations of complement component 3 (C3) in the EA group compared to the control group. Structural and antioxidant gene transcripts in articular cartilage were increased by EA. There was no significant difference in total joint histology scores between groups. CONCLUSION: This study provides evidence that EA has a positive effect on symptom, but not disease, modification in a rodent model of OA. Further investigations into mechanistic pathways that may explain the efficacy of EA in this animal model are needed.

Age- and sex-associated differences in hematology and biochemistry parameters of Dunkin Hartley guinea pigs (Cavia porcellus).

The Dunkin Hartley is the most common guinea pig strain used in biomedical research, particularly for studies of asthma, allergy, infectious disease, reproduction, and osteoarthritis. Minimally invasive blood tests, such as complete blood counts and serum biochemistry profiles, are often collected for diagnostics and laboratory analyses. However, reference intervals for these assays have not yet been well-documented in this strain. The purpose of this study was to establish reference intervals for hematologic and biochemical parameters of Dunkin Hartley guinea pigs and determine age- and sex-related differences. Hematologic and biochemical parameters were retrospectively obtained from 145 male and 68 female guinea pigs between 2 and 15 months of age. All blood parameters were analyzed by a veterinary clinical pathology laboratory. Reference intervals were established according to the American Society for Veterinary Clinical Pathology guidelines. Age- and sex-related differences were determined using unpaired t-tests or nonparametric Mann-Whitney tests. Hematocrit, red blood cell distribution width, mean platelet volume, white blood cell count, heterophils, monocytes, eosinophils, glucose, blood urea nitrogen, creatinine, calcium, magnesium, total protein, albumin, globulin, cholesterol, aspartate aminotransferase, gamma glutamyl transferase, and bicarbonate increased with age. Mean corpuscular hemoglobin concentration, cellular hemoglobin concentration mean, platelets, lymphocytes, phosphorus, albumin/globulin ratio, alkaline phosphatase, anion gap, and calculated osmolality decreased with age. Males had higher hemoglobin, hematocrit, red blood cell count, mean corpuscular hemoglobin concentration, white blood cell count, heterophils, Foa-Kurloff cells, alanine aminotransferase, and bicarbonate and lower mean corpuscular volume, red blood cell distribution width, platelets, mean platelet volume, eosinophils, total protein, albumin, globulin, cholesterol, potassium, anion gap, calculated osmolality, and iron compared to females. Establishing age and sex differences in hematologic and biochemical parameters of Dunkin Hartley guinea pigs provides valuable insight into their physiology to better evaluate diagnostics and experimental results.